Polyene antibiotics have been known for a number of years. However, most of them have a low solubility in water which limits their use and, more important, they have a haemolytic action on red blood cells and are so toxic that their clinical use is either prevented or very restricted.
The polyene antibiotics constitute a wide category of substances which are normally produced by the metabolism of various microorganisms of the Streptomyces species. Having regard to their unsaturated structure containing conjugated double bonds, they are divided into groups, such as the hexaenes, the pentaenes and, of particular importance, the heptaenes and the tetraenes, each group being characterised by its own ultra-violet absorption spectrum, which serves as an important means of structural elucidation.
Although the formulae of these substances are, in most cases, unknown or have only been partially elucidated, the substances are known to have a macrolide structure; as far as the physico-chemical characteristics are concerned, these substances are generally amphoteric; sometimes they are characterised by the presence of only one functional group, which may be acidic or basic.
Very few examples of esters of natural polyenic substances have been reported in the literature. As far as we know, the few such derivatives which have been reported are all methyl esters.
Consequently, there is clearly a great need for an improved method for preparing esters of the polyene antibiotics which have the same desirable properties as the natural antibiotic without suffering from the disadvantages thereof, such as toxicity and haemolytic activity.
Using the polyenic, amphoteric or acidic antibiotics as starting materials, we have found that the corresponding alkyl esters can readily be obtained therefrom. Detailed analytical investigations of the natural polyenes have shown that they often consist of a mixture of several substances with similar structures so it is obvious that they can be esterified as such as mixtures or separately, when the individual constituents are available.